Cytotoxic clerodane diterpenoids from fruits of Casearia grewiifolia

Bioactivity-guided fractionation of the ethyl acetate-soluble fraction of a methanol extract of the fruits of Casearia grewiifolia afforded eight new clerodane diterpenes, caseargrewiins E-L (1-8), and a known clerodane diterpene, esculentin B (9). The structures of 1-8 were established on the basis of 1D and 2D NMR spectroscopic data. Most of these compounds exhibited cytotoxicity against three cancer cell lines with IC50 values in the range 0.15-6.00 microg/mL.     

New cytotoxic clerodane diterpenoids from the leaves and twigs of Casearia membranacea

Bioassay-guided fractionation of an EtOAc-soluble extract of Casearia membranacea has resulted in the isolation of six new clerodane diterpenes, caseamembrins A-F (1-6), and a known compound, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (7). The structures of 1-6 were established on the basis of extensive 1D and 2D NMR spectroscopic analysis. In addition, the new derivatives, 8 and 9, were prepared by acylation of 7 and 3, respectively. The isolated diterpenoids and their derivatives were tested against human prostate (PC-3) and hepatoma (Hep3B) cancer cells. Compounds 1, 3-5, and 7 exhibited cytotoxicity against both tumor cells, with IC(50) values below 3 micromicro, while compounds 2, 6, 8, and 9 were less effective.     

Cytotoxic clerodane diterpenes from Casearia rupestris

Four new clerodane diterpenes, casearupestrins A-D (1-4), were isolated from the leaves of Casearia rupestris. Compounds 1 and 4 were acetylated to yield 2,7-di-O-acetylcasearupestrin A (5) and 2,6-di-O-acetylcasearupestrin D (6). All compounds were evaluated for cytotoxicity against a small panel of human cancer cell lines. Casearupestrin A (1) exhibited the most potent activity against MDA/MB-435 (human melanoma) and SF-295 (human glioblastoma) cells, superior to that of the standard drug doxorubicin.     

Cytotoxic clerodane diterpenoids and their hydrolysis products from Casearia nigrescens from the rainforest of Madagascar

Bioassay-guided fractionation of the cytotoxic leaf and flower extract of Casearia nigrescens led to the isolation of four new clerodane diterpenoids, designated caseanigrescens A-D (1-4). These compounds were subject to hydrolysis to dialdehydes when stored in CDCl3. The structures of compounds 1-4 were determined using 1D and 2D NMR spectroscopy. All four compounds showed moderate cytotoxicity to the A2780 human ovarian cancer cell line, with an IC50 range of 0.83-1.4 microM.     

New bioactive clerodane diterpenoids from the bark of Casearia grewiifolia

Bioactivity-guided fractionation of hexane and dichloromethane extracts of the bark of Casearia grewiifolia afforded four new clerodane diterpenes, caseargrewiins A-D (1-4), and two known clerodane diterpenes, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-methoxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (5) and rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (6). The structures of 1-4 were established on the basis of the interpretation of their 1D and 2D NMR spectral data. The absolute configuration of 4 was determined by the modified Mosher's method. All compounds exhibited promising antimalarial and antimycobacterial activities but also cytotoxicity against three cancer cell lines.     

Novel bioactive clerodane diterpenoids from the leaves and twigs of Casearia sylvestris

Fractionation of a methanol extract of the leaves and twigs of Casearia sylvestris, as directed by activity against KB cell cytotoxicity, led to the isolation of three novel clerodane diterpenoids, casearvestrins A-C (1-3). The structures of 1-3 were deduced from one- and two-dimensional NMR experiments, including relative stereochemical assignments based on ROESY correlations and COSY coupling constants. All three compounds displayed promising bioactivity, both in cytotoxicity assays against a panel of tumor cell lines and in antifungal assays via the growth inhibition of Aspergillus niger in a disk diffusion assay.     

Structure and stereochemistry of new cytotoxic clerodane diterpenoids from the bark of Casearia lucida from the Madagascar rainforest

Bioassay-guided fractionation of a CH(2)Cl(2)/MeOH extract of the bark of Casearia lucida resulted in the isolation of 11 new clerodane diterpenes, namely, casearlucins A-K (1-11), and three known clerodane diterpenoids, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-hydroxy-2-(2xi-methylbutanoyloxy)cleroda-3,13(16),14-triene (12), rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-methoxy-2-(2xi-methylbutanoyloxy)cleroda-3,13(16),14-triene (13), and rel-(2S,5R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-2-(2xi-methylbutanoyloxy)cleroda-3,13(16),14-triene (14). The structures of compounds 1-11 were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. All compounds exhibited cytotoxicity activity against the A2780 ovarian cancer cell line, but none of the six compounds selected for testing in multiple cell lines showed significant selectivity.     

Four new clerodane diterpenoids from Callicarpa pentandra

Leaf extracts of Callicarpa pentandra provided four new clerodane-type diterpenoids (1-4), of which 1, 2, and 4 have ring-A-contracted structures. Their structures and stereochemistry were established by spectral data interpretation, and for 3 also by single-crystal X-ray diffraction.     

Cytotoxic diterpenoids from Sapium insigne

Chemical investigation into the twigs and leaves of Sapium insigne afforded seven new diterpenoids, sapinsignoids A-G (1-7), together with 10 known diterpenoids. The structures of 1-7 were assigned on the basis of detailed spectroscopic analysis and chemical degradation. Compounds 1-4 exhibited significant cytotoxicity against the A-549 tumor cell line (IC(50) 0.2-1.8 μM), while compounds 1-3 showed moderate cytotoxicity against the HL-60 cell line (IC(50) 2.7-6.5 μM).     

Cytotoxic diterpenoids from Euphorbia helioscopia

Four new jatrophane-type diterpenoids (1-4), together with 16 known related compounds, were isolated from the Chinese medicinal plant Euphorbia helioscopia. The structures of 1-4 were determined on the basis of spectroscopic and chemical methods. Cytotoxicity of the isolated compounds against HeLa and MDA-MB-231 cells was evaluated, with only helioscopinolide A (5) and euphornin (3a) being active.     

Echinophyllins C-F, new nitrogen-containing clerodane diterpenoids from Echinodorus macrophyllus

Four new nitrogen-containing clerodane diterpenoids, echinophyllins C-F (1-4), were isolated from the leaves of the Brazilian medicinal plant Echinodorus macrophyllus ("Chapéu-de-couro"), and their structures and relative stereochemistry were elucidated from their spectroscopic data. Compounds 1-4 possess an alpha,beta-unsaturated gamma-lactam ring consisting of a clerodane diterpene unit and an amine moiety.     

Cytotoxic diterpenoids and sesquiterpenoids from Pteris multifida

Three new ent-kaurane diterpenoids, named pterokaurane M 1-M 3 ( 1- 3) and three new C 14 pterosin-sesquiterpenoids, named multifidoside A-C ( 4- 6), along with 18 known compounds, were isolated from the whole plants of Pteris multifida . The structures of 1- 6 were established using spectroscopic methods, including extensive 2D NMR and CD analyses. Compounds 4 and 5 showed cytotoxicity against the HepG2 tumor cell line with IC 50 values of less than 10 microM.     

Porwenins A and B, new clerodane diterpenoids from Portulaca okinawensis.

Two new clerodane-type diterpenes, porwenins A (1) and B (2), were isolated from Portulaca okinawensis, and the structures were elucidated by spectroscopic data.     

Cytotoxic diterpenoids from the soft coral Sarcophyton crassocaule

Five new cembrane diterpenoids, sarcrassins A-E (1-5) along with a known compound, emblide (6), have been isolated from the soft coral Sarcophyton crassocaule collected from the Bay of Sanya, Hainan Island, China. The structures of 1-5 were determined by spectroscopic methods including 1D and 2D NMR techniques. Their relative configurations were determined by NMR data and NOESY experiments. Compounds 2, 4, and 6 exhibited significant cytotoxic activities against KB cell lines with IC50 values of 5.0, 4.0, and 5.0 microg/mL, respectively, while compounds 1 and 5 showed moderate cytotoxicity toward KB cell lines with IC50 values of 19.0 and 13.0 microg/mL, respectively.     

Cytotoxic diterpenoids from the soft coral Sinularia microclavata

The soft coral Sinularia microclavata collected from the bay of Sanya, Hainan Island, China, yielded a new diterpenoid, microclavatin (1), and a known cembranolide, capillolide (2). The structure of compound 1 was determined on the basis of spectroscopic methods and X-ray single-crystal diffraction analysis. Microclavatin (1) showed cytotoxic activities against tumor cell lines KB and MCF with IC50 values of 5.0 and 20.0 microg/mL, respectively, and capillolide (2) showed potent cytotoxic activity against tumor cell lines (A-549) with an IC50 value of 0.5 microg/mL.     

Cytotoxic xenia diterpenoids from the soft coral Xenia umbellata

Eleven new xenia diterpenoids, umbellacins A-G (1-7), 14,15-epoxy-xeniolide H (8), 3-acetyl-14,15-epoxy-xeniolide H (9), and umbellacins H and I (10, 11), were isolated from a methylene chloride-soluble fraction of the soft coral Xenia umbellata. The structures were elucidated by extensive spectroscopic analysis, and their cytotoxicity against selected cancer cells was measured in vitro.     

Cytotoxic 3,20-epoxy-ent-kaurane diterpenoids from Isodon eriocalyx var. laxiflora

Four new ent-kaurane diterpenoids, laxiflorins J-M (1-4), along with maoecrystal A (5) and maoecrystal P (6), were isolated from the leaves of Isodon eriocalyx var. laxiflora. Their structures were determined by spectroscopic analyses. All the compounds were assayed for their cytotoxic effects on human tumor K562, A549, and T24 cell lines. Compounds 1 and 6 showed significant inhibitory effects on human tumor K562 and T24 cells, with IC(50) values less than 0.5 microg/mL. Compound 3 also demonstrated cytotoxic activities against all three types of human tumor cells, with IC(50) values in the range of 1-25 microg/mL.     

Cytotoxic diterpenoids from the bark of Pseudolarix kaempferi and their structure-activity relationships

Four new diterpenoids, 11S-deacetylpseudolaric acid A (2), deacetylpseudolaric acid A O-beta-d-glucopyranoside (3), deacetylpseudolaric acid A 2,3-dihydroxypropyl ester (4), and deacetylpseudolaric acid B 2,3-dihydroxypropyl ester (5), and nine known diterpenoids were isolated from the bark of Pseudolarix kaempferi. Their structures were determined on the basis of chemical and spectroscopic analyses. In addition, their in vitro cytotoxic activities against three human cancer cell lines and their structure-activity relationships were evaluated.     

Cytotoxic diterpenoids from the hybrid soft coral Sinularia maxima x Sinularia polydactyla

Chemical investigation of the hybrid soft coral Sinularia maxima x Sinularia polydactyla yielded four new cembranolide diterpenes (1-4), the norcembranoid 5-episinuleptolide (5), and two known sesquiterpenes. The structures and configurations of the new compounds were determined by spectroscopic techniques and comparison of NMR data with those of related metabolites. Compound 3 shows strong cytotoxicity on the breast cancer SK-BR3 cell line and cervix cancer HeLa and HeLa-Apl cell lines with GI(50) values of 0.039, 0.48, and 0.56 microM, respectively.     

Novel cytotoxic diterpenes from Casearia arborea

Cytotoxicity-guided fractionation of the dichloromethane-methanol extract of the roots of Casearia arborea yielded five novel clerodane diterpenes, casearborins A-E (1-5), as well as cucurbitacin B. The presence of cucurbitacins glycosides was also detected. The absolute configuration of casearborin E was determined by X-ray crystallography.